Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL.

Abstract:

:To study the role of the BH3 domain in mediating pro-apoptotic and anti-apoptotic activities of Bcl-2 family members, we identified a series of novel small molecules (BH3Is) that inhibit the binding of the Bak BH3 peptide to Bcl-xL. NMR analyses revealed that BH3Is target the BH3-binding pocket of Bcl-xL. Inhibitors specifically block the BH3-domain-mediated heterodimerization between Bcl-2 family members in vitro and in vivo and induce apoptosis. Our results indicate that BH3-dependent heterodimerization is the key function of anti-apoptotic Bcl-2 family members and is required for the maintenance of cellular homeostasis.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Degterev A,Lugovskoy A,Cardone M,Mulley B,Wagner G,Mitchison T,Yuan J

doi

10.1038/35055085

keywords:

subject

Has Abstract

pub_date

2001-02-01 00:00:00

pages

173-82

issue

2

eissn

1465-7392

issn

1476-4679

journal_volume

3

pub_type

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